Alveolar epithelial cells (AEC) contribute to lung injury responses by proliferating, regulating matrix resorption, and presenting active TGF(31 to fibroblasts, promoting their conversion to myofibroblasts. AEC may also exercise their own plasticity to become fibroblast-like in their invasiveness and matrix production. However, regulation of cellular responses to TGFP1 and the potential of AEC to undergo epithelial to mesenchymal-like transitions (EMT) in the lung are poorly understood. While TGFP1 signaling is critical to these processes, TGFbl signaling alone appears insufficient to effect fibrogenesis. Recentfindings show that epithelial cell EMT responses to TGFbt require b1 integrins and especially the integrin a3b1. These observations lead to the hypothesis that pi integrins act as a critical sensor in TGFP1 signaling. It isfurther proposed that in AEC cc3p1, a laminin receptor, is the key regulatory pi integrin which mediates TGFP1 driven epithelial cell plasticity and mesenchymaltransition in the context of lung matrix remodeling. This hypothesis is addressed in the application through a series of studies which use either RNAi knockdown or alveolar epithelial cells with inducible deletion of a3(31via ere recombinase to elucidate how integrins regulate SMAD signaling. The presence of EMT in models of murine fibrogenesis in vivo will be examined in mice expressing either galactosidase or EGFP selectively in lung epithelial cells and the role of o3p1 in the process defined by studies of fibrogenesis in mice with conditional deletion of AEC aspl. Elucidation of a pathway of integrin signaling controlling AEC responsesto TGFP1 and definition of the capacity of AEC to transition to fibroblasts during matrix remodeling should provide new insight into the pathobiology of pulmonary fibrosis.